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Cancer studies: Investigation fails to replicate results of most lab research

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The reliability of early-stage cancer biology research is called into question by an investigation that concludes more than half of experimental results can’t be replicated by independent scientists



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7 December 2021

Lab-based cancer research isn’t always easy to replicate, according to a new investigation

Anthony Kwan/Bloomberg via Getty Images

An eight-year-long investigation into the reliability of preclinical cancer biology research has found that fewer than half of the results published in 23 highly cited papers could be successfully reproduced.

Tim Errington, director of research at the Center for Open Science in Virginia – which conducted the investigation – says the original plan was to reproduce 193 experiments from 53 papers. But, as explained in one of two studies the team publishes today, this was reduced to 50 experiments from 23 papers.

“Just trying to understand what was done and reported in the papers in order to do it again was really hard. We couldn’t get access to the information,” he says.

In total, the 50 experiments included 112 potentially replicable binary “success or failure” outcomes. However, as detailed in the second study published today, Errington and his colleagues could replicate the effects of only 51 of these – or 46 per cent.

The experiments were all in-vitro or animal-based preclinical cancer biology studies, and didn’t include genomic or proteomic experiments. They were from papers published between 2010 and 2012 and were selected because they were all “high-impact” studies that had been read and heavily cited by other researchers.

The results are “a bit eye-opening”, says Errington.

The investigation’s findings do, however, align with those of earlier reports published by the big pharmaceutical companies Bayer and Amgen. C. Glenn Begley, who recently co-founded US biotech Parthenon Therapeutics, was a senior cancer biologist at Amgen and an author of its report, which was published in 2012.

“We looked back at the papers that we had relied upon at Amgen and found that we could only reproduce 11 per cent of the studies,” says Begley.

The Amgen report was applauded by some in the research community for shining a light on an important problem. But Begley says the report was also criticised for a lack of openness about exactly which studies it tried and failed to replicate.

This criticism can’t be levelled at the new investigation. Errington and his colleagues have published all the data about the studies they included on the Open Science Framework, a website and data repository run by the Center for Open Science, to help facilitate data sharing. They also invited peer review of their methods for replication before the study was completed.

Although the investigation focused on preclinical studies, the replicability problems it uncovered might help explain problems with later-stage studies in people too. For instance, a previous survey of the industry showed that less than 30 per cent of phase II and less than 50 per cent of phase III cancer drug trials succeed.

Even if there isn’t a direct link between the problems at the preclinical and clinical trial stages of scientific investigation, Errington says the high rate of failure of later clinical trials in this area is very concerning.

“At that point, you’ve already invested in the very expensive clinical trial pipeline,” he says. “This is people’s lives, hopes and livelihood on the line here.”

He adds that the Center for Open Science is now advocating for a scientific culture change that places more focus on data sharing and good quality early-stage studies, which could help highlight any issues with replicability employed in this sort of research.

Emily Sena at the University of Edinburgh, UK, agrees this is important, but says more needs to be done to persuade scientists to get on board. “It requires institutions and their appointment panels and promotion panels to value the fact that you have done this, but the incentive structure just isn’t there at the moment,” she says.

There are promising signs of change on the horizon. The US National Institutes of Health, one of the largest funders of health-related research, is instituting a new policy in early 2023 that will make data sharing the default for the projects it funds. Several journals have also changed their publishing systems in recent years to encourage open science and data sharing.

Begley says he has seen a real change in the decade since he co-authored the Amgen report. “When I first started talking about this issue, people would get very angry and say, ‘Well, this just proves that Amgen scientists are incompetent’,” he says. “Now, when I give a talk, the focus is on what should we be doing about this.”

Journal references: eLife, DOI: 10.7554/eLife.67995  and DOI: 10.7554/eLife.71601

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Solar storms may cause up to 5500 heart-related deaths in a given year

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In an approximate 11-year cycle, the sun blasts out charged particles and magnetised plasma that can distort Earth’s magnetic field, which may disrupt our body clock and ultimately affect our heart



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17 June 2022

A solar storm

Jurik Peter/Shutterstock

Solar storms that disrupt Earth’s magnetic field may cause up to 5500 heart-related deaths in the US in a given year.

The sun goes through cycles of high and low activity that repeat approximately every 11 years. During periods of high activity, it blasts out charged particles and magnetised plasma that can distort Earth’s magnetic field.

These so-called solar storms can cause glitches in our power grids and bring down Earth-orbiting satellites. A handful of studies have also hinted that they increase the risk of …

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UK Covid infection rate rising, with more than a million cases in England | Coronavirus

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Coronavirus infections are rising in the UK, figures have revealed, with experts noting the increase is probably down to the more transmissible BA.4 and BA.5 Omicron variants.

The figures from the Office for National Statistics (ONS), based on swabs collected from randomly selected households, reveal that in the week ending 11 June an estimated one in 50 people in the community in England are thought to have had Covid – around 1.13 million people.

The figure is even higher, at one in 45, in both Wales and Northern Ireland, while it was highest in Scotland where, in the week ending 10 June, one in 30 people are thought to have been infected.

While the figures remain below the peak levels of infection seen earlier this year, when around one in 13 people in England had Covid, the findings are a rise on the previous week where one in 70 people in England were thought to be infected. Furthermore, the data reveals increases in all regions of England, except the north-east, and across all age groups.

Experts say that a key factor in the increase is probably the rise of the Covid variants of concern BA.4 and BA.5.

“Infections have increased across all four UK nations, driven by rising numbers of people infected with the BA.4 and BA.5 Omicron variants,” said Kara Steel, senior statistician for the Covid-19 Infection Survey.

While Steel said it remained too early to say if this was the start of another wave, others have warned it may already have begun, with increased mixing and travelling among other factors fuelling a rise in cases.

Among concerns scientists have raised are that BA.4, BA.5 and another variant on the rise, BA.2.12.1, replicate more efficiently in human lung cells than BA.2.

Prof Azra Ghani, an epidemiologist at Imperial College London, said the latest figures were not surprising, and might rise further.

“This increase in infection prevalence is likely due to the growth of the BA.4 and BA.5 Omicron subvariants, which as we have seen elsewhere in Europe, appear to be able to escape immunity generated from previous Omicron subvariants,” she said.

“It is therefore possible that we will continue to see some growth in infection prevalence in the coming weeks and consequently an increase in hospitalisations, although these subvariants do not currently appear to result in any significantly changed severity profile. This does however serve as a reminder that the Covid-19 pandemic is not over.”

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NHS to offer women in England drug that cuts recurrence of breast cancer | Breast cancer

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Thousands of women in England with breast cancer are to benefit from a new pill on the NHS which reduces the risk of the disease coming back.

The National Institute for Health and Care Excellence (Nice) has given the green light to abemaciclib, which cuts the chance of breast cancer returning after a patient has had surgery to remove a tumour.

Trials showed that patients who had the drug with hormone therapy had a more than 30% improved chance of their cancer not coming back after surgery, compared with hormone therapy alone.

“It’s fantastic thousands of women with this type of primary breast cancer will now have an additional treatment option available on the NHS to help further reduce the risk of the disease coming back,” said Delyth Morgan, the chief executive of charity Breast Cancer Now.

“The fear of breast cancer returning or spreading to other parts of their body and becoming incurable can cause considerable anxiety for so many women and their loved ones.

“New effective treatments such as abemaciclib, which can offer more women the chance to further reduce the risk of the disease recurring, are therefore extremely welcome and this is an important step change in the drug options available for this group of patients.”

The twice-a-day pill is suitable for women with hormone receptor-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence who have had surgery. About 4,000 women will benefit initially, Nice said.

Helen Knight, the interim director of medicines evaluation at Nice, said the draft recommendation came less than a month after abemaciclib received its licence.

“The fact that we have been able to produce draft recommendations so quickly is testament to the success of our ambition to support patient access to clinically and cost effective treatments as early as possible,” said Knight. “Until now there have been no targeted treatments for people with this type of breast cancer.

“Abemaciclib with hormone therapy represents a significant improvement in how it is treated because being able to have a targeted treatment earlier after surgery will increase the chance of curing the disease and reduce the likelihood of developing incurable advanced disease.”

Abemaciclib works by targeting and inhibiting proteins in cancer cells which allow the cancer to divide and grow. It normally costs £2,950 for a packet of 56 150mg-tablets, but the manufacturer, Eli Lilly, has agreed an undisclosed discounted price for NHS England.

“Thanks in part to this latest deal struck by NHS England, NHS patients will be able to access another new targeted drug for a common and aggressive form of breast cancer,” said Prof Peter Johnson, the cancer director of NHS England.

“Abemaciclib, when used alongside a hormone therapy, offers a new, doubly targeted, treatment option, helping to increase the chances of beating the cancer for good, as well as meeting the NHS’s commitment to delivering improved cancer care under our long-term plan.”

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